This grant application is for 5 years of funding through the Mentored Patient Oriented Research Career Development Award (K23) program. The objective is to develop the candidate's skills in behavioral genetics research and augment her training in neurobiological endophenotypes of bipolar disorder. The research plan builds on the candidate's experience in behavioral endophenotypes and neurocognition in major mental illness (schizophrenia and bipolar disorder); its basic aim is to assess familial aggregation of measures of neurocognitive function, temperament, and neuroanatomy in unaffected relatives of individuals with severe bipolar disorder, and apply these measures to quantitative trait loci (QTL) analysis. The proposed study will provide an important first step toward the ultimate goal of linking bipolar endophenotypes to specific genes. Both the research and training plan are opportunistic, utilizing previously ascertained study samples from ongoing research, and renowned investigators in the UCLA research community. The Career Development Plan will develop the Pi's skills in: 1) the design of studies that collect and analyze human genetic material, 2) data analytic methods used to examine genetic effects on cognition and neuroanatony, and 3) analysis of quantitative trait loci. Methods of career development include: 1) the proposed study, 2) the mentorship of Drs. Nelson Freimer and Tyrone Cannon , 3) consultation with experts in behavioral and statistical genetics, 4) formal coursework in statistical genetics methodology and brain mapping, 5) attendance at scientific meetings, and 6) data preparation for submission of manuscripts to peer-reviewed journals. Given the candidate's prior training, proposed mentorship, outstanding resources and research environment, a K23 award will allow her to become a successful and independent investigator in the genetics and neurobiological bases of bipolar disorder. [unreadable] [unreadable]